再分化使能的 TSHRCART 细胞克服侵袭性甲状腺癌中的抗原丢失
Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.
这些发现确立了肿瘤再分化作为一种可推广的策略,用于克服抗原丢失并增强 CAR-T 细胞疗法在甲状腺癌以及可能其他实体瘤中的疗效。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Therapeutic treatments targeting communication between angiogenic and immune microenvironments in thyroid cancers.
Therapeutic treatments targeting communication between angiogenic and immune microenvironments in thyroid cancers.
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近年来,特异性靶向疗法(如BRAF V600E抑制剂或高选择性RET抑制剂)、抗血管生成药物(如酪氨酸激酶抑制剂〔TKI〕)和免疫检查点抑制剂的引入,改变了甲状腺癌的治疗格局,并显著改善部分患者的结局。由于原发性或继发性肿瘤耐药机制及毒性特征,靶向和抗血管生成治疗的疗效通常短暂且有限。免疫治疗策略目前已取得初步结果。本文综述并前瞻性讨论非髓样和髓样甲状腺癌的免疫微环境,以及其与血管生成微环境(内皮细胞和周细胞)的相互作用,并探讨如何通过联合治疗靶向这些相互作用。此外,本文回顾CAR-T 细胞治疗在晚期甲状腺癌中提供更持久、有效应答的潜力。总之,甲状腺癌的血管生成和免疫微环境在功能上相互联系。采用毒性可耐受的抗血管生成药物和免疫检查点抑制剂,并联合特异性靶向抑制剂,可能克服耐药并比单药治疗取得更好的临床结局。
Thyroid cancer treatment has recently been revolutionized by the introduction of specific targeted therapies (e. g. BRAF V600E or highly selective RET inhibitors), anti-angiogenic agents (e. g. tyrosine kinase inhibitors (TKIs)) and immune checkpoint inhibitors, which significantly ameliorate outcomes in selected groups of thyroid cancer patients.
Targeted and anti-angiogenic treatments are characterized by transient and partial efficacy, due to primary or secondary tumor resistance mechanisms, and toxicity profile. Immune therapy-based approaches are producing preliminary results.
Herein, we review and prospectively discuss immune microenvironment in non-medullary and medullary thyroid cancers and its interplays with angiogenic microenvironment (endothelial cells and pericytes).
In addition, we discuss how these interactions might be targeted using combined therapies.
Furthermore, we will review chimeric antigen receptor (CAR) T cells treatment that potentially may ensure a more durable and effective response in advanced thyroid cancers. In sum, angiogenic and immune microenvironments show functional connectivity in TCs. Therapies with anti-angiogenic and immune checkpoint inhibitors combined with specific targeted therapy inhibitors with a tolerable toxicity profile may overcome drug resistance and provide better clinical outcomes than single agents.
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